Patients (pts) with advanced SCLC have a rapid relapse after 1L treatment, and only one approved agent (topotecan) for 2L treatment. Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) plus toripalimab (T, an anti-PD-1 antibody) has exhibited encouraging efficacy in a neuroendocrine carcinoma cohort in a trial evaluating S + T in pts with selected solid tumors. Here, we report the safety and efficacy results in the SCLC cohort.
In this cohort of the multicenter, multi-cohort, single-arm phase 2 study (NCT04169672), adults (18-75) with advanced SCLC who had failed 1L systemic chemotherapy (platinum-based systemic chemotherapy) were eligible, and received 3-week cycles of S (250 mg orally, QD) plus T (240 mg IV, Q3W). The primary endpoint was objective response rate (ORR) per RECIST 1.1.
At cutoff date (Aug 1, 2021), 20 pts (median age, 58 yrs; ECOG=1, 17 pts; PD-L1 CPS<1, 16 pts) were enrolled and received combination treatment. Median treatment duration of S and T was both 3 mo. Among pts with at least one post-baseline tumor assessment (evaluable pts, n=19), the confirmed ORR (2 PRs) was 10.5% (95%CI 1.3-33.14), DCR was 94.7% (95%CI 73.97-99.87). Median DoR was not reached. Median PFS (mPFS) was 2.96 mo (95%CI 2.79-4.11), and median OS (mOS) was 10.94 mo (95%CI 4.96-NR). In platinum-sensitive (n=8) and -resistant (n=12) subgroups (defined as pts with disease relapsed ≥90 days and <90 days, respectively, after platinum-based chemotherapy), the confirmed ORR (95%CI) in evaluable pts (n=8 and 11) were 0 and 18.2% (2.28-51.78), DCR (95%CI) were 87.5% (47.35-99.68) and 100% (71.51-100), respectively; mPFS (95%CI) were 3.4 mo (1.38-5.59) and 2.96 mo (2.69-4.11), and mOS (95%CI) were not reached (median duration of follow up, 11.10 mo) and 8.87 mo (4.34-NR), respectively. Nine (45%) pts reported TRAEs of grade ≥3, most commonly (≥2 pts) with hypertriglyceridemia and hypertension, both with 2 pts. No TRAEs led to treatment discontinuation or death.
S + T showed a promising anti-tumor activity and an acceptable toxicity for 2L treatment of SCLC. The combination of the two agents might be a novel 2L therapeutic option for SCLC.
Clinical trial identification
We acknowledge Xia Yin (medical writer of HUTCHMED) for the abstract editing work.
Legal entity responsible for the study
J. Zhou, H. Shi, P. Tan, S. Fan, W. SuFinancial Interests, Personal, Full or part-time Employment: HUTCHMED. All other authors have declared no conflicts of interest.